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Le virus de la fièvre hémorragique de Crimée-Congo (VFHCC) est un Nairovirus appartenant à la famille des Bunyaviridae, responsable d’une maladie hémorragique sévère chez l’Homme, associée à des symptômes non spécifiques et à une forte mortalité. La transmission se fait par morsure de tique ou par contact direct avec des fluides corporels contaminés. N’ayant ni vaccin ni traitement spécifique, un apport de connaissances sur les interactions cellulaires VFHCC-hôte ainsi que sur les mécanismes développés en réponse à l’infection est nécessaire.Nous avons tout d’abord étudié le potentiel antiviral de molécules sur la réplication du VFHCC. La chloroquine et la chlorpromazine ont été identifiées et inhibent efficacement la réplication virale avec une protection induite chez la souris contre l’infection, en particulier en combinaison avec la ribavirine.De nombreux virus sont connus pour être ciblés par, ou pour détourner la voie de l’autophagie. Nous avons regardé si l’infection par le VFHCC était associée à une modulation de l’autophagie et si la réplication virale était impactée par l’activité autophagique. L’étude de cellules hépatocytaires et épithéliales a montré une mobilisation massive du LC3, principal marqueur des vésicules autophagiques, par le VHFCC. Celle-ci reflète une induction du flux autophagique d’un nouveau type, n’impliquant pas les voies classiques de recrutement du LC3. La réplication virale n’est pas directement modulée par cette autophagie atypique mais des effets indirects sont à étudier. La plupart de ces observations ont été montrées pour le Nairovirus Dugbe avec cependant une cinétique différente.Le dernier axe étudié porte sur l’analyse de l’impact des IFITMs, facteurs de restriction virale connu pour interférer avec les processus de fusion membranaire, sur la réplication du virus Dugbe. L’étude a révélé une inhibition de la réplication virale par certains IFITMs.Des études supplémentaires portant sur l’interaction virus-cellule hôte et les mécanismes moléculaires associés sont nécessaires pour mieux comprendre la physiopathologie induite par le VFHCC et mettre au point de nouvelles stratégies thérapeutiques. / Crimean-Congo hemorrhagic fever virus (CCHFV) belongs to Nairovirus genus and to Bunyaviridae family. It is responsible for a severe hemorrhagic disease in humans, associated with non-specific symptoms and high lethality. Transmission is made by tick’s bite or by direct contact with contaminated body fluids. Since no vaccines or treatments are available, there is a need to accumulate knowledge on all aspects of CCHFV-host cell interaction as well as on response mechanisms that are taking place during infection.We first investigated pharmacological ways to interfere with CCHFV replication. Chloroquine and chlorpromazine (known modulators of some viral infections) were efficiently inhibiting viral replication and induce a protection in mice against CCHFV infection, particularly in the presence of ribavirin. Since several viruses are targeted by, or take advantage of, the autophagy response of infected cells, we explored whether CCHFV infection was associated with modulation of autophagy and whether virus replication was impacted by the autophagic activity of infected cells. By using hepatocytes and epithelial cells, we found that CCHFV induced a massive mobilization of the major marker of autophagic vesicles LC3. This mobilization reflected an induced autophagy flux and was of a novel type since known pathways of LC3 recruitment were not involved. The replication of CCHFV was indeed not directly modulated by this atypical form of autophagy but indirect effects remain to be studied. Most of these observations were found to be valid for the related, Dugbe virus (DUGV) with however, a distinct kinetic.Finally, we analyzed whether DUGV was sensitive to the IFITMs, restriction factors that can interfere with membrane fusion processes. Studies revealed that DUGV replication could be inhibited by some IFITMs. Additional studies on virus host-cell interactions and their associated molecular mechanisms should help to better understand the physiopathology induced by CCHFV and to devise therapeutic strategies.

Conservative international thought in Victorian Britain is a prominent landmark in the landscape of international thought which has up to now gone unmapped. In illuminating this body of thought, the thesis addresses weaknesses present in three different historiographies. As the first detailed study of conservative international thought in Victorian Britain, the thesis rectifies a marked bias in Victorian intellectual history towards the study of liberal and radical thought. Furthermore, by analysing the political thought of major representatives of the conservative educated classes, this thesis provides context for the history of conservative high politics, thereby leading us to view these in a different light. Finally, this study, by providing a historically nuanced account of the evolution of major themes of international relations theory in mid-Victorian Britain, functions as a corrective to the self-history of the academic field of International Relations. The thesis makes its argument by analysing conservative contributions in periodicals, pamphlets, and newspapers to British public debates on international affairs, from the Crimean War (1854-56) until the Eastern Question crisis of 1876-80. The general claim of this thesis is that there existed a distinctly conservative perspective on the international sphere. The core elements of this conservative perspective were the primacy of statesmen in setting foreign policy; of interests, military force, and stature in determining the course of international politics; and of order and equilibrium as its normative content. Conservative authors used this constellation of ideas in the major debates of the mid-Victorian era on international affairs, both as a means to make sense of events, and as a counterpoint to liberal narratives - with which Victorian international thought is all too often identified. In recovering the international political thought of Victorian conservatives, this thesis illuminates an important but neglected aspect of how international relations were understood and conceptualised in mid-Victorian Britain.

<p>Abstract</p><p>Crimean-Congo Hemorrhagic Fever virus (CCHF) and Lassa virus are giving sources illness to humans. In addition to zoonotic transmission, CCHF and Lassa virus can spread from person to person. After a short incubation period, CCHF and Lassa virus infections are characterized by a sudden onset of high fever, chills, headache and cough just like flu. Even some people are vomiting and have diarrhoea. After a few days of illness hemorrhagic manifestations occur. Treatment options for CCHF and Lassa viruses are limited, and there is no vaccine available for use in humans. The purpose of the present study was to produce recombinant nucleocapsid protein of Lassavirus and CCHF virus including an aminoterminal His-tag by a Semliki Forest Virus Replicon (pSFV 4.2). The recombinant proteins are planned to be used in future development of diagnostic methods.</p>

Abstract Crimean-Congo Hemorrhagic Fever virus (CCHF) and Lassa virus are giving sources illness to humans. In addition to zoonotic transmission, CCHF and Lassa virus can spread from person to person. After a short incubation period, CCHF and Lassa virus infections are characterized by a sudden onset of high fever, chills, headache and cough just like flu. Even some people are vomiting and have diarrhoea. After a few days of illness hemorrhagic manifestations occur. Treatment options for CCHF and Lassa viruses are limited, and there is no vaccine available for use in humans. The purpose of the present study was to produce recombinant nucleocapsid protein of Lassavirus and CCHF virus including an aminoterminal His-tag by a Semliki Forest Virus Replicon (pSFV 4.2). The recombinant proteins are planned to be used in future development of diagnostic methods.

This thesis analyses how three television stations - Czech ČT24, Russian RT and American CNN - informed about the Crimean crisis which took place in Ukraine in 2014. The first part of the thesis presents theoretical approach and mentions previous similar studies, which focused on examining of medial coverage and framing of war conflicts. Next chapter describes the history of Ukraine briefly and underlines events which could have caused the Crimean crisis. Thereafter the thesis introduces the timeline of the Crimean crisis. In the next part the thesis analyses sources, topics and keywords which appeared in the news of ČT24, RT and CNN. It also describes how particular people and events were visually covered. In the final chapter the approach of the three examined television channels is compared.

The great variation displayed by nucleic acid molecules in human cells, and the continuous discovery of their impact on life, consequently require continuous refinements of molecular analysis techniques. Padlock probes and rolling circle amplification offer single nucleotide discrimination in situ, a high signal-to-noise ratio and localized detection within cells and tissues. In this thesis, in situ detection of nucleic acids with padlock probes and rolling circle amplification was applied for detection of DNA in the single cell gel electrophoresis assay to detect nuclear and mitochondrial DNA. This assay is used to measure DNA damage and repair.  The behaviour of mitochondrial DNA in the single cell gel electrophoresis assay has earlier been controversial, but it was shown herein that mitochondrial DNA diffuses away early in the assay. In contrast, Alu repeats remain associated with the nuclear matrix throughout the procedure. A new twelve gel approach was also developed with increased throughput of the single cell gel electrophoresis assay. DNA repair of three genes OGG1, XPD and HPRT and of Alu repeats after H2O2 induced damage was further monitored. All three genes and Alu repeats were repaired faster than total DNA. Finally, padlock probes and rolling circle amplification were applied for detection of the single stranded RNA virus Crimean Congo hemorrhagic fever virus. The virus was detected by first reverse transcribing RNA into cDNA.. The virus RNA together with its complementary RNA and the nucleocapsid protein were detected in cultured cells. The work presented here enables studies of gene specific damage and repair as well as viral infections in situ. Detection by ligation offers high specificity and makes it possible to discriminate even between closely related molecules. Therefore, these techniques will be useful for a wide range of applications within research and diagnostics.

Geographically, Pakistan is in the western part of south Asia at about 24-37 °N latitudes and62-75 °E longitudes. Livestock and agriculture are two major sectors in Pakistan and play animportant role in the country economy.The tick infestation in livestock is not only devastating for animals and their products but alsobecome the cause of transmission of pathogens into humans. Crimean Congo fever (CCHF) isa viral tick-borne fatal disease. The dissemination of ticks and amplification of Crimean Congofever (CCHF) pathogen throughout the tick-animals-tick cycle, increases risk of transmissionto humans many times. In Pakistan, cases are reported in all areas, particularly those areaswhich lie on the border to CCHF endemic countries. There is a high prevalence of CCHF inboth Baluchistan and Khyber Pakhtunkhwa regions. Baluchistan is bordering with Afghanistanand Iran and Khyber Pakhtunkhwa with Afghanistan. Linear regression analysis revealed apositive significant association of high level of CCHF cases in livestock, with camels, goatsand sheep. The literacy rate is negatively significantly corelated with the numbers of cases.Statistical analysis of border effect revealed a high positive significant correlation of CCHFprevalence in areas near to borders. Both Baluchistan and Khyber Pakhtunkhwa (KPK) haslow literacy rate than other regions of Pakistan. Islamabad (capital city) has a higher literacyrate than all other regions but there is still a high CCHF prevalence. This is not only becauseof high population density but people from other regions, particularly from Baluchistan andKPK come here for animals selling or to seeking medical facilities in the large city hospitals.The study gives a proof that illiteracy and borders are the major respondent factors in theCCHF incidences and prevalence in an area. There is a need to raise awareness about ticksand tick-borne disease in the public and establishment of monitoring system across the bordersto prevent the spread of CCHF virus.

Until 2008, almost two decades since the end of the cold war, Russia still retained old Soviet military structures. Steady opposition by the Russian generals against military modernization and reforms was finally broken in relation with the poor performance of Russian forces during the Russia-Georgian war in 2008. The process of modernization commenced in the following years has important security implications for post-Soviet countries. We could observe the new abilities of the Russian military during the seizure of the Crimean peninsula in 2014. Russian forces had been considered an ineffective institution with outdated military technology where corrupt practices were the rule rather than the exception. As we could see in 2008 Georgia Russian forces depended on numerical superiority and blunt military force. On the other hand during the Crimean events of 2014 the Russian military conducted the whole operation with high level of professionalism, without any bloodshed, and with modern weaponry. This research is based on the theory of neorealism which defines key parameters for performing a military modernization analysis. These include numbers, effectivity and strategy of military forces that help us to determine the current strength and power of each state. Therefore this research focuses on the...

On a small contested part of the world, the peninsula of Crimea, once a part of the former Soviet Union, lives a people who have endured genocide and who have struggled to etch out an identity in a land once their own. They are the Crimean Tatar. Even their name, an exonym promoting the Crimeans’ “peripheral status” (Powell) and their ensuing “cultural schizophrenia” (Vizenor), bears witness to the otherization they have withstood throughout centuries. However, despite attempts to relegate them to the history books, Crimeans are alive and well in the “motherland,” but not without some difficulty. Having been forced to reframe their identities because of numerous imperialistic, colonialist, and soviet behavior and policies, there have been many who have resisted, first and foremost through rhetorical sovereignty, the ability to reframe Crimean Tatar identity through Crimean Tatar rhetoric. This negotiation of identity through rhetoric has included a fierce defense of their language and culture in what Malea Powell calls a “war with homogeneity,” a struggle for identification based on resistance. This thesis seeks to understand the rhetorical function of naming practices as acts that inscribe material meaning and perform marginalization or resistance within the context of Crimea-L, a Yahoo! Group listserv as well as immediate and remote Crimean history. To analyze the rhetoric of marginalization and resistance in naming practices, I use the Discourse Historical Approach (DHA) to Critical Discourse Analysis (CDA) within recently archived discourses. Ruth Wodak’s DHA strategies will be reappropriated as Naming Practice Strategies, depicting efforts in otherization or rhetorical sovereignty.